摘要目的:分析中国范科尼贫血（FA）的临床特征和分子诊断现状。方法:回顾性分析中国造血干细胞移植和中国儿童造血干细胞移植登记组2009年8月至2022年1月收录的107例FA患儿的一般情况、临床特征以及染色体断裂实验和基因检测结果；根据变异类型将FANCA基因突变患儿分为轻型和重型突变组，并采用Wilcoxon秩和检验比较组间表型差异。结果:176例登记FA患儿中，69例（39.2%）因缺乏明确的基因诊断结果而被剔除，余来自15家医院的107例患儿纳入本研究，包括男70例、女37例，移植治疗年龄6（4，9）岁。入组患儿涉及10个致病基因，包括89例FANCA基因、7例FANCG基因、3例FANCB基因、2例FANCE基因以及FANCC、FANCD1、FANCD2、FANCF、FANCJ和FANCN基因各1例；69.2%（72/104）的患儿表现为复合杂合或纯合功能丧失型变异。FANCA基因变异中79.2%（141/178）为功能丧失型变异，且外显子大缺失占比20.8%（37/178）。51.4%的患儿（55/107）有染色体断裂检测记录，阳性率81.8%（45/55）。80例患儿的172个先天性畸形中，牛奶咖啡斑（16.3%，28/172）、拇指畸形（16.3%，28/172）、多指（13.9%，24/172）和矮小（12.2%，21/172）是FA患儿较常见的先天性畸形。50例重型与26例轻型FANCA基因突变突变患儿相比，先天性畸形数差异无统计学意义（ Z=-1.33， P=0.185）。 结论:FANCA基因是FA患儿最主要的致病基因，临床需加强对其外显子缺失的检测，不同FANCA基因变异类型患儿之间未见表型差异；染色体断裂检测有助于变异致病性判定，但其精准性有待提升。

abstractsObjective:To analyze the clinical and molecular diagnostic status of Fanconi anemia (FA) in China.Methods:The General situation, clinical manifestations and chromosome breakage test and genetic test results of 107 pediatric FA cases registered in the Chinese Blood and Marrow Transplantation Registry Group (CBMTRG) and the Chinese Children Blood and Marrow Transplantation Registry Group (CCBMTRG) from August 2009 to January 2022 were analyzed retrospectively. Children with FANCA gene variants were divided into mild and severe groups based on the type of variant, and Wilcoxon-test was used to compare the phenotypic differences between groups.Results:Of the 176 registered FA patients, 69 (39.2%) cases were excluded due to lack of definitive genetic diagnosis results, and the remaining 107 children from 15 hospitals were included in the study, including 70 males and 37 females. The age at transplantation treatment were 6 (4, 9) years. The enrolled children were involved in 10 pathogenic genes, including 89 cases of FANCA gene, 7 cases of FANCG gene, 3 cases of FANCB gene, 2 cases of FANCE gene and 1 case each of FANCC, FANCD1, FANCD2, FANCF, FANCJ, and FANCN gene. Compound heterozygous or homozygous of loss-of-function variants account for 69.2% (72/104). Loss-of-function variants account for 79.2% (141/178) in FANCA gene variants, and 20.8% (37/178) were large exon deletions. Fifty-five children (51.4%) had chromosome breakage test records, with a positive rate of 81.8% (45/55). There were 172 congenital malformations in 80 children.Café-au-Lait spots (16.3%, 28/172), thumb deformities (16.3%,28/172), polydactyly (13.9%, 24/172), and short stature (12.2%, 21/172) were the most common congenital malformations in Chinese children with FA. No significant difference was found in the number of congenital malformations between children with severe (50 cases) and mild FANCA variants (26 cases) ( Z=-1.33, P=0.185). Conclusions:FANCA gene is the main pathogenic gene in children with FA, where the detection of its exon deletion should be strengthened clinically. There were no phenotypic differences among children with different types of FANCA variants. Chromosome break test is helpful to determine the pathogenicity of variants, but its accuracy needs to be improved.